Renoprotective effects of dual treatment with dihydrotestosterone and an aromatase inhibitor in male streptozotocin (STZ)‐induced diabetic rats

Our previous data showed that streptozotocin (STZ)‐diabetic males have increased estradiol (E) and decreased testosterone (T) levels that correlate with renal injury. Supplementing dihydrotestosterone (DHT) or inhibiting E biosynthesis in these diabetic rats was partially renoprotective. The aim of this study was to examine if a concomitant therapy of DHT supplementation and E inhibition provides full renoprotection. The study was performed in male STZ‐diabetic (D), STZ‐diabetic supplemented with 0.75mg/day DHT (Dt), STZ‐diabetic treated daily with an aromatase inhibitor anastrozole, 0.15mg/kg (Da) and STZ‐diabetic that had combined therapy of DHT and anastrozole (Dta) for 12 weeks. Urine albumin excretion (UAE) was determined by ELISA and calculated by measuring urine albumin concentration and daily urine output. Glomerulosclerosis (GSI) and tubulointerstitial fibrosis (TIFI) indices were graded using a semiquantitative scoring method. Markers of inflammation (IL‐6) and basement membrane thickening (collagen type IV) protein expression were determined by Western blot and normalized to total β‐actin. Our data suggest that combined treatment of DHT and an aromatase inhibitor reduced diabetes‐associated increases in UAE GSI, TIFI and further decreased the amount of IL‐6 and collagen type IV protein expression. Our results suggest that supplemental DHT along with blocking aromatase activity in males provides a more superior therapy than either treatment alone. Supported by RO1DK075832Group UAE (mg/day) GSI (AU) TIFI (AU) IL‐6 (ROD) Collagen Type IV (ROD)D 50.6±5.3 # 2.2±0.1 # 1.8±0.2 # 1.59±0.05 # 0.64±0.06 # Dt 21.9±3.5 *, # 1.6±0.2 *, # 1.0±0.1 *, # 0.99±0.03 *, # 0.36±0.02 *, # Da 21.5±1.4 *, # 1.5±0.2 *, # 1.1±0.1 *, # 0.98±0.04 *, # 0.37±0.01 *, # Dta 7.2±0.8 * 0.8±0.2 * 0.7±0.1 * 0.81±0.02 * 0.22±0.02 *Avg±SEM; * P<0.05 vs. D; # P<0.05 vs. Dta